Clinical Features

• Lungs
  • Asthma - cardinal feature (95%), often severe or steroid-dependent, with steroids often masking other signs of disease
  • Other findings (in 50-70%): pulmonary opacities with eosinophilia, pleural effusion (often eosinophilic), nodules that are rarely cavitary, alveolar hemorrhage
• Upper airway
  • Allergic rhinitis, chronic rhinosinusitis with nasal polyps
  • Chronic serous otitis and sensorineural hearing loss are occasionally seen in CSS and likely reflect the severity of sinusitis (necrotizing lesions as with Wegener's is unusual)
• Skin
  • Tender subcutaneous (granulomatous) nodules on the extensor surfaces of the arm, particularly the elbows, hands, and legs occur in up to 2/3rds of patients during the vasculitic phase
  • Skin lesions can also appear as palpable purpura, a macular or papular erythematous rash, and hemorrhagic lesions, ranging from petechiae to extensive ecchymosis
• Other
  • CV - heart failure, effusion, valvular abnormalities, arrhythmia
  • CNS - peripheral neuropathy
  • Renal - renal insufficiency, glomerulonephritis
  • GI - eosinophilic gastroenteritis

Usually occurs in sequential phases

Phase	Age	Features
Prodromal	20-30's	Late-onset asthma and allergic rhinitis Very rarely occurs in children
Eosinophilic		Blood eosinophilia, eosinophilic infiltration of lungs, GI tract, skin, and other organs 40% may progress to vasculitic phase
Vasculitic	30-40's	Life-threatening systemic vasculitis of small-medium vessels Often accompanied by skin findings and constitutional symptoms (fever, weight loss, fatigue) Cardiac symptoms are cause of death in 50%

Diagnosis

American College of Rheumatology Criteria (1990) - a patient shall be said to have CSS if at least 4/6 criteria are positive (sensitivity 85%/specificity 99.7%)

Asthma Blood eosinophilia >10% Neuropathy, mono or poly Pulmonary infiltrates, non-fixed Paranasal sinus abnormality Extravascular eosinophils on blood vessel biopsy

• Laboratory tests
  • Eosinophilia - usually 5000-9000, but >1500 or 10% should prompt suspicion; often suppressed by systemic steroids
  • ANCA - found in 40-60% of patients; majority (70-75%) of ANCA positive will have MPO-ANCA or pANCA
    • Negative ANCA may correlate with different natural course of CSS
  • Nonspecific abnormalities:
    • Elevated ESR or CRP
    • Elevated IgE level
    • Hypergammaglobulinemia
    • RF positive at low titer
    • Normal or elevated complement (C3, C4, CH50) levels
    • Urinalysis abormalities
• Imaging
  • CXR - often demonstrate diverse findings
    • Usually transient and patchy opacities (75%) without lobar or segmental distribution
    • Pleural effusions (30%) are usually exudative and eosinophilic
  • HRCT - typical findings include patchy parenchymal consolidation or ground glass opacification, nodules may also be noted
• Other: PFTs, bronchoscopy/BAL, surgical biopsy of involved skin/nerve/lung site, EKG, echocardiogram, cardiac MRI

Differential Diagnosis

• AERD - may overlap clinically with prodromal phase of CSS
• ABPA - only affects sinopulmonary sites
• Eosinophilic pneumonia - usually isolated to lungs, usually lack granulomas on biopsy
• Hypereosinophilic syndrome
• Wegener's granulomatosis - usually not associated with marked eosinophilia and asthma, and ANCA is typically anti-PR3 (cANCA)
• Microscopic polyangiitis - usually not associated with marked eosinophilia and asthma

References